The growth of marrow or spleen grafts is affected by immune responses and by other interactions not part of conventional immune responses. To study these, assays for the earliest precursor cells -those with the most proliferative capacity - are needed. We are developing a competitive repopulation assay that measures long-term functioning of immunohemopoietic grafts, to supplement conventional CFU-S assays. Grafts with genetically defined antigenic differences are used in immunologically intact genetically anemic recipients that are populated by normal stem cells. Comparisons of marrow and skin grafts, preimmunization with different tissues, and skin grafting of marrow chimeras determine antigen distributions and effects of immune responses. Quantitative measures of the inhibitory or stimulatory effects of immune responses on stem cell growth and functioning are provided by comparing competitive repopulating abilities of antigenically disparate grafts in immune competent anemic and immune suppressed irradiated recipients. Resistance to parental marrow grafts by F1 hybrids breaks the conventional laws of transplantation. It is especially strong in certain strains that we use and, in W-anemic recipients, long-term, systemic hybrid resistance occurs that is abrogated by age and irradiation. The competitive repopulation assay is very useful for studying long-term systemic hybrid resistance. Hybrid and allogeneic resistance will be further studied in these systems and in vitro, where natural killer (NK) cells may be part of the same phenomenon. Abrogation and restoration of the effect, resistance against nonhemopoietic stem cells, whether resisted cells are killed, and attempted separations of cells responsible for recognition and reaction will be studied in long- and short-term systems in vivo and in vitro, comparing the same genotypes in all systems.